All organisms contain a biological clock which allows them to maintain daily rhythms in the absence of environmental stimuli. These circadian rhythms affect almost every aspect of animal behavior and underlie well known human phenomena such as jet lag and the problems encountered by shift workers. In addition, malfunctions in the circadian timing system could contribute to disease states such as sleep dysfunction and seasonal affective disorders. It is now widely accepted that the mammalian circadian clock is located in the suprachiasmatic nuclei of the hypothalamus (SCN), and that the neurons of the SCN show circadian rhythms in their electrical activity. Less well understood, however, is the cellular basis for such rhythmicity. The experiments in this project will use electrical recording from mouse SCN neurons both in brain slices and in dispersed cultures to determine how the electrical properties of these cells change during the daily cycle. The goal is to identify voltage-gated currents that display circadian rhythms in their activity and are therefore likely to regulate the rhythmicity in the firing patterns of SCN neurons. Agents that phase-shift the activity of the SCN in vitro will be used to demonstrate that the rhythms of these circadian currents are indeed correlated with the rhythm of the SCN as a whole. The knowledge gained from these experiments will provide further insights into the nature of the mammalian circadian clock and could advance the development of clinically effective therapies for human circadian disorders.